Cancer is a heterogeneous disease characterized by the accumulation of tumor cells, which can cause the death of both animals and humans. Conventional methods of treating cancer include surgical treatments, the administration of chemotherapeutic agents, and recently immune response based therapy which involve the administration of an antibody or antibody fragment which may be conjugated to a therapeutic moiety. However, to date, such treatments have been of limited success.
Despite all its limitations, chemotherapy is one of the most extended methods for the treatment of different types of cancer. Thus, the development of new antitumoral therapies of general applicability is one of the main goals in medicinal chemistry.
The incapacity of chemical drugs to distinguish between normal cells that divide rapidly and the tumoral ones, can lead to the patient depression of the immune system. This has been considered one of the main problems of chemotherapy, as well as the mechanisms of resistance developed by cancer cells, which include the inactivation of p53 pathway. Although most drugs currently used in cancer therapy induce apoptosis of these cells, at least partially, through activation of the p53 pathway, p53 protein is mutated in half of all cancers analyzed, demonstrating its importance in cancer development.
Big efforts are being made in the improvement of antitumoral treatments, trying to achieve active and selective compounds that could act independently of p53 pathway, to be given to patients with incipient and recurrent cancer or metastasis.
The presence of thiazole rings is common in many natural bioactive compounds, especially with antitumoral properties. These compounds such as cyclopeptides, polyheterocyclic alkaloids, and compounds of mixed biosynthetic origin display a remarkable structural diversity and often present bis- tris- and 5 polithiazole arrangements. The biosynthetic origin of these substructural units is related to cyclodehydration processes promoted by the thiol of a cysteine and the neighbouring peptide bond. However, the synthetic access to these natural compounds is often complicated, either by peptide-solid phase synthesis, condensation protocols (Hantszch synthesis) or by means of transition metal couplings from thiazole precursors.
Some bisthiazole compounds with capacity of inhibiting cell proliferation have been described in the art. In WO 2004/016622 some 4,4′-bipyridiyl-2,2′-bisoxazoles and 4,4′-bipyridyl-2,2′-bisthiazoles with antiproliferative activity are described, in particular, against HT-29 cells.
However, despite the research efforts invested in the past, at present there is no curative therapy for most types of cancer, therefore there is still a need to find effective antitumoral agents. In particular, antitumoral therapies which act independently of p53 would be of great interest.